Biomedical subjects
Publications and source records attributed to M Satake.
A new analog of yessotoxin, 1-desulfoyessotoxin, was isolated from the digestive glands of mussels growing in the Sognefjord, Norway. Its structure was determined by NMR and negative ion CID MS/MS experiments. 1-Desulfoyessotoxin can be detected by the fluorometric HPLC method analogous with other yessotoxins.
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1. Desensitization of ET(A) endothelin receptor (ET(A)R) was compared between the rat and guinea-pig with regard to negative chronotropic response (NC) in the right atria (RA). 2. ET-1 (100 nM) produced distinct NC in the presence of BQ788 (300 nM), and positive chronotropic response (PC) in the presence of BQ123 (1 microM) in both species, showing that ETAR and ET(B) endothelin receptor (ET(B)R) mediate NC and PC, respectively. 3. Repetitive applications of ET-1 (50 nM) desensitized PC, and the second application only induced a strong NC in both species. Later applications of ET-1 produced virtually no response in the rat RA, whereas they produced BQ123-sensitive NCs repetitively in guinea-pig RA, exhibiting marked species difference in desensitization of ETAR-mediated NC. 4. Pretreatment with staurosporine (100 nM) prevented desensitization of ET(A)R in the rat RA altogether. However, phorbol 12-myristate 13-acetate (PMA, 300 nM) failed to induce, but rather hampered, desensitization of ET(A)R. 5. Partial amino acid sequencing of ET(A)Rs, spanning from the 2nd through the 4th intracellular loops, revealed that all the potential Ser/Thr phosphorylation sites, including a protein kinase C (PKC) site, are conserved among guinea-pigs, rats, rabbits, bovines and humans. 6. In guinea pig RA, pretreatment with okadaic acid (1 microg ml(-1)) and PMA did not facilitate desensitization of ET(A)R whereas these agents successfully desensitized ETAR during combined stimulation of beta-adrenoceptor and ET(A)R by isoproterenol (300 nM) and ET-1 (100 nM). 7. These results suggest that species differences in desensitization of ET(A)R are not caused by differences in the site(s) of, but caused by differences in the environment for phosphorylation of the receptor. Desensitization of ET(A)R appears to require phosphorylation of the receptor by PKC as well as a kinase stimulated by beta-adrenoceptor activation.
To obtain immunomodulating substances from Amazonian medicinal plants, hot water extracts from 21 samples available commercially were tested in terms of mitogenic and colony-stimulating factor (CSF)-inducing activities. Among them, Dalbergia monetaria exhibited the highest CSF-inducing activity. Orobol 8-C-glucoside (OCG-8) and orobol 6-C-glucoside (OCG-6) were isolated from the bark of D. monetaria as major constituents. The CSF-inducing activity of OCG-8 was higher than that of OCG-6 and a dose-dependent manner at a range of 0.1-10 mg/mouse. Serum CSF production induced by an intraperitoneal (i.p.) injection with 1 mg OCG-8 reached a peak at 4-6 h later, suggesting that OCG-8 would act on hematopoietic system.
In vitro studies of human NK cell-mediated cytotoxicity and ADCC against porcine target cells were performed. Stimulation of human PBMC responder cells with either allogeneic or xenogeneic porcine cells led to a marked increase in NK cell reactivity. Maximum reactivity was reached following 3-6 days of in vitro culture. The sensitivity of target cells ranked as follows: K562 > porcine PHA-induced lymphoblasts > resting porcine PBMC. Limiting dilution analysis showed that allo- and xeno-stimulation in vitro led to differentiation of similar frequencies of effector NK cells. Split culture experiments showed that single NK effector cells were cytotoxic against both K562 and porcine lymphoblasts, demonstrating that individual NK cells lack species specificity. NK effector cell generation stimulated by xenogeneic cells was cyclosporin A (CsA) sensitive and dependent on the presence of autologous responder T lymphocytes, a dependence that was completely reconstituted by the sole addition of human IL-2. Xenostimulation of enriched CD3+ cells also led to a preferential appearance of CD16+ or CD56+ lymphoblasts. Natural xenoreactive human anti-porcine antibodies are mainly of IgM and IgG2 subclasses, but antibodies in xenoimmunised patients reactive against porcine lymphocytes and fetal porcine islet cells were also of IgG1 and IgG3 subclasses. The same subclass distribution was found among antibodies specific for gal(alpha)1,3 gal epitopes as shown by tests performed with alpha1,3 galactosyltransferase-transfected Raji cells (human Burkitt lymphoma cells). Natural antibodies did not mediate ADCC, whereas gal(alpha)1,3 gal-specific antibodies in sera from xenoimmunised patients did. Fetal porcine islet cells were sensitive to human NK cell-mediated cytotoxicity and to ADCC mediated by xenoimmune sera.
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The Kampo medicine Shichimotsu-koka-to (SKT) is used to treat hypertension and atherosclerosis in Japan. The action of SKT was studied, focusing on nitric oxide, which is intimately involved in regulation of blood pressure and cell functions associated with atherogenesis and inflammation. Oral administration of SKT enhanced serum nitric oxide (NOx) levels dose-dependently and 3 d administration was enough to detect its effect. The maximal level of serum NOx was maintained at around 27 microM, a concentration which did not result in harmful effects on cells. On the other hand, L-arginine, the substrate of NO synthase (NOS), was also increased by SKT administration. When the source of L-arginine was studied, only 12.7 mg of L-arginine was contained in 1 g of SKT and this amount of L-arginine could not explain the increased L-arginine levels in serum. These results suggest that SKT may enhance serum L-arginine by acting on L-arginine metabolism, but not by supplying L-arginine itself, resulting in enhancement of serum NOx. In conclusion, the antihypertensive and antiatherosclerotic action shown by SKT may be in part due to enhanced serum NOx, thus suggesting that SKT may become a unique orally active drug for cardiovascular diseases as a new NO donor.
The present study was carried out to compare the accelerating effect of shikonin and alkannin and to elucidate the expression of CD antigen and histological changes on the proliferation of granulation tissue in rats. Shikonin and alkannin produced a dose-dependent acceleration of the cotton pellet-induced granuloma formation and this accelerating potency of both compounds on the proliferation of granulation tissue was about the same 5 and 10 d after implantation of the cotton pellet. Also, both compounds increased the ratio of CD11b+ cells in the granulation tissue 5 and 10 d after implantation of the cotton pellet. Both compounds increased the expression of CD11b+ cells with granulocytes such as macrophages and histiocytes, and then accelerated the proliferation of fibroblasts and collagen fiber. On the other hand, neither compound increased the ratio of CD3+ cells in the granulation tissue after 5 and 10 d. These results suggest that shikonin and alkannin accelerate the proliferation of granulation tissue induced by the cotton pellet and this accelerating effect may be attributed to an increase in the expression of CD11b+ cells, and the acceleration of the proliferation of fibroblasts and collagen fiber in the granulation tissue.
Shichimotsu-koka-to (SKT) has been prescribed to treat patients with essential and renal hypertension. We investigated the effects of SKT on renal lesions in stroke-prone spontaneously hypertensive rats (SHRSPs). SHRSPs were given an extract of SKT by mixing it with drinking water, from 8 through 29 weeks of age, so that the average intake of SKT extract was about 1.5 g/kg/d. At 29 weeks of age, the kidneys of SHRSPs exhibited proliferative arteritis characterized by the proliferation of smooth muscle cells in the interlobular arteries, dilation and degeneration of renal tubules, infiltration of inflammatory cells and hemorrhage, with partial swelling or necrotizing of glomeruli. In particular, arteritis and periarteritis were noted. The treatment of SHRSPs with SKT ameliorated this morphological damage in the kidney and significantly decreased urea nitrogen in the serum. Treatment with SKT also strongly decreased the xanthine oxidase (XOD) activity and significantly increased the superoxide dismutase (SOD) activity in the kidney of SHRSPs; consequently, these values became close to those in normotensive Wistar Kyoto rats (WKYs). These results indicate that treatment with SKT ameliorated the histopathological damage and change in activity of enzymes related to free radicals in the kidney of SHRSPs, which may be important mechanisms for SKT for protecting SHRSPs from renal dysfunction.
The pharmacokinetics of norephedrine enantiomers were determined after the independent i.v. administration of (+/-)-norephedrine (20 mg/kg), (-)-norephedrine (10 mg/kg), and (+)-norephedrine (10 mg/kg) to rats. Significant differences were observed in the pharmacokinetic parameters of each enantiomer when the enantiomers were administered singly and as a racemate. For example, the values of total body clearance (Cltot) and urinary excretion clearance (Clr) of (-)-norephedrine administered as a racemate were higher than those of the norephedrine enantiomer administered singly. The areas under the curve of concentration versus time (AUC) of (-)-norephedrine administered as a racemate had a tendency to increase. While Cltot of (+)-norephedrine administered as a racemate showed a lower value and AUC showed a higher value. The value of Clr of (+)-norephedrine administered as a racemate showed a tendency to decrease. There was no difference in the in vitro serum protein binding of (-)- and (+)-norephedrine. The data from this study reveal that pharmacokinetic interactions exist between the norephedrine enantiomers and also reveal that the serum protein binding is not concerned with those interactions. The differences in the pharmacological effects after the individual administration of (-)-norephedrine or (+/-)-norephedrine may be coused by the differences in their concentrations in the plasma.
Recently, herbal remedy and health caring food are widely used throughout the generation. These main plant materials have been characterized and classified into 5 categories, by the Ministry of Health and Welfare (MHW), Japanese Government, in 1971, which include 3 medicine divisions and 2 food divisions. These categories, having only limited number of plants, were quite difficult to classify the newly imported plant materials. In order to solve this problem, each category was updated to include new herbal materials in March 1998. Kampo medicines are Japanese traditional medicines, which has been used for the patients mostly by doctors of western medicine and 3 kinds of Kampo prescription had been reevaluated by the drug reevaluation system of Japan. But, along with the expanding consumption of the Kampo medicines in the clinical treatments, several side effects of the Kampo medicines has recently been reported by the collection of adverse reaction data of MHW, these side effects are important signals for believing the safety of natural drugs. The chapter I is definition of medicinal plant and crude drugs, and chapter II is reported of WHO guidelines for the traditional medicines. Chapter III is 4 section; 1. safety of the medicinal plants and crude drugs is included the poisonous plant and the side effect of Kampo medicines, 2. the pesticide for the crude drugs in Japanese Pharmacopoeia, 3. limited test of contamination of microorganisms, 4. Identification of medicinal plant names. Chapter IV is the definition of drugs and food. The chapter V is the drugs type materials used in young generation for hallucinogenic or sexual purpose. Chapter VI is the stance to research work for the new drugs from plant gene resources in the world.
Aristolochic acids are nitrophenanthrenes with a carboxylic acid fanction which have been found only among the Aristolochiaceae. In 1993, rapidly progressive interstitial renal fibrosis has been reported in women have been on a slimming regimen including Chinese herbal medicines in Belgium. In Japan, at the Kansai district, several cases of Chinese herbs nephropathy have been reported quite recently. In both cases, aristolochic acids was detected in the Chinese herbal medicines taken by the patients. We have Asiasarum Root, a species of Aristolochiaceae, in Japanese Pharmacopoeia. Therefore, we quantitatively analysed aristolochic acids in these herbal medicines and related plants.
OBJECTIVE: To probe into the morphology and distribution characteristics of calcium oxalate crystals in several kinds of Cinnamon bark. METHOD: Forty samples of ten different species of Cinamomi Cortex were examined, and the inter-cellular calcium oxalate crystals in the phloem rays were observed by optical microscope and scanning electron microscope. RESULT: It was found that for samples of the same botanical origin, there is little variation in the crystal morphology following certain regularity. The amount, size and ultra-micromorphologic characteristics are influenced by various factors. CONCLUSION: The pattern of morphology and distribution of calcium oxalate crystals may well be an index for identification of the crude drug of Cinnamon bark.
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We present the cases of two patients with subacute onset of multifocal painful neuropathy with spontaneous remission and no relapse. The distribution of pain in patient 1 was hands (median > ulnar nerve region) and feet (peroneal and terminal tibial nerve regions), and in patient 2, hands (ulnar nerve region) and feet, left worse than in right. Both patients experienced facial numbness. Deep tendon reflexes were intact except for absent ankle jerks in patient 2. Motor nerve conduction studies demonstrated a marked prolongation of the distal motor latencies with normal proximal segment conduction velocities, suggesting distal demyelination. Cerebrospinal fluid protein concentration was elevated in patient 2, but no definite abnormality was found on sural nerve biopsy. A demyelinating neuropathy with a monophasic self-limited course may be consistent with Guillain-Barre syndrome (GBS). However, the multifocal painful sensory symptoms with facial numbness and the marked distal nerve conduction slowing in our cases are not consistent with GBS.
The Pebpb2/Cbfb gene encodes the non-DNA binding beta subunit of the heterodimeric transcription factor, PEBP2/CBF, and has been implicated in a subtype of human acute myeloid leukemia, as well as being indispensable for the development of definitive hematopoiesis in the murine fetal liver. By examining a subcellular localization of the PEBP2beta/CBFbeta protein in tissue culture cells, we could reveal an additional aspect of the protein other than to be a subunit of a transcription factor. Immunoblot and immunocytochemical staining showed that PEBP2beta/CBFbeta was mostly present in the cytoplasm. This PEBP2beta/CBFbeta was free from its DNA-binding partner, the alpha subunit of PEBP2/CBF, as judged by the electrophoretic mobility shift assays. Furthermore, a significant amount of PEBP2beta/CBFbeta was retained in the cytoskeleton preparation after detergent extraction of the cells and was found by double immunofluorescence to colocalize with the F-actin on stress fibers and the vinculin in membrane processes. Thus, the present study extends PEBP2beta/CBFbeta to be a cytoskeleton-affinitive as well as nuclear protein. The implications of these results are discussed.